Control of infectious mortality due to carbapenemase-producing Klebsiella pneumoniae in hematopoietic stem cell transplantation.

Carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) infections are an emerging cause of death after hematopoietic stem cell transplantation (HSCT). In allogeneic transplants, mortality rate may rise up to 60%. We retrospectively evaluated 540 patients receiving a transplant from an auto- or an allogeneic source between January 2011 and October 2015. After an Institutional increase in the prevalence of KPC-Kp bloodstream infections (BSI) in June 2012, from July 2012, 366 consecutive patients received the following preventive measures: (i) weekly rectal swabs for surveillance; (ii) contact precautions in carriers (iii) early-targeted therapy in neutropenic febrile carriers. Molecular typing identified KPC-Kp clone ST512 as the main clone responsible for colonization, BSI and outbreaks. After the introduction of these preventive measures, the cumulative incidence of KPC-Kp BSI (P=0.01) and septic shocks (P=0.01) at 1 year after HSCT was significantly reduced. KPC-Kp infection-mortality dropped from 62.5% (pre-intervention) to 16.6% (post-intervention). Day 100 transplant-related mortality and KPC-Kp infection-related mortality after allogeneic HSCT were reduced from 22% to 10% (P=0.001) and from 4% to 1% (P=0.04), respectively. None of the pre-HSCT carriers was excluded from transplant. These results suggest that active surveillance, contact precautions and early-targeted therapies, may efficiently control KPC-Kp spread and related mortality even after allogeneic HSCT.

Endomyocardial biopsy technique for orthotopic heart transplantation and cardiac stem-cell harvesting.

INTRODUCTION: Orthotopic heart transplantation (OHT) is performed using the bicaval and pulmonary venous anastomoses or the standard (biatrial) anastomoses. The special considerations of endomyocardial biopsy after OHT using the bicaval technique, and after myocardial infarction for harvesting of cardiac stem cells, have not been described. METHODS: When approached via the right or left internal jugular vein, important technical considerations were ultrasound guidance for vascular access; a soft, 80-cm, 0.035-inch, J-tipped guidewire; a long (23-cm), 7-Fr sheath; and a flexible 7-Fr, 50-cm bioptome. These technical aspects were helpful to avoid disruption of the superior vena cava suture line, avoid entry into the right atrial appendage or coronary sinus, avoid right ventricular free wall perforation, and provide ready access to the right ventricular septal wall. We used the same principles and technical considerations when obtaining the cardiac stem cells after myocardial infarction in patients enrolled in the CADUCEUS trial. RESULTS: From January 2002 to December 2005, 754 biopsy procedures were performed in 179 patients after OHT with the bicaval technique, using bioptome A. There was 1 occurrence of ventricular fibrillation requiring cardioversion, and no occurrence of cardiac tamponade during the procedure. From January 2006 to September 2013, 2818 biopsy procedures were performed in 1064 patients using bioptome B. No patient developed ventricular fibrillation or cardiac tamponade during the procedure. In 2010 and 2011, 23 biopsy procedures were performed in 23 patients after acute myocardial infarction, using bioptome B. No immediate complications occurred while performing these biopsies. The late occurrence of tricuspid regurgitation was not evaluated in this study. CONCLUSIONS: Endomyocardial biopsy procedures can be safely performed after OHT with the bicaval technique and after myocardial infarction for harvesting of cardiac stem cells. Ultrasound guidance for vascular access, a long guidewire and sheath, and a flexible bioptome are important features for the safe conduct of the biopsy procedure.

Haemorrhagic cystitis in haematopoietic stem cell transplantation (HSCT): a prospective observational study of incidence and management in HSCT centres within the GITMO network (Gruppo Italiano Trapianto Midollo Osseo).

UNLABELLED: Haemorrhagic cystitis (HC) is a recognised complication in patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT). This study evaluates the incidence and severity of HC in patients undergoing allogeneic HSCT during hospitalisation and within the first 100 days following transplant, looking at the use of prophylaxis, management of HC, outcomes at 100 days post transplant, and to identify any correlations between development of HC and the different conditioning regimens for transplant or HC prevention methods used. RESULTS: Four hundred and fifty patients (412 adult and 38 paediatric) were enrolled in this prospective, multicentre, and observational study. HC was observed in 55 patients (12.2%) of which 8/38 were paediatric (21% of total paediatric sample) and 47/412 adults (11.4% of total adult sample). HC was observed primarily in the non-related HSCT group (45/55; 81.8%, p= 0.001) compared to sibling and myeloablative transplant protocols (48/55; 87.3%; p= 0.008) and with respect to reduced intensity conditioning regimens (7/55;12.7%). In 33 patients with HC (60%), BK virus was isolated in urine samples, a potential co-factor in the pathogenesis of HC. The median day of HC presentation was 23 days post HSCT infusion, with a mean duration of 20 days. The most frequent therapeutic treatments were placement of a bladder catheter (31/55; 56%) and continuous bladder irrigation (40/55; 73%). The range of variables in terms of conditioning regimens and so on, makes analysis difficult. CONCLUSIONS: This multi-centre national study reported similar incidence rates of HC to those in the literature. Evidence-based guidelines for prophylaxis and management are required in transplant centres. Further research is required to look at both prophylactic and therapeutic interventions, which also consider toxicity of newer conditioning regimens.

Antithymocyte globulin induction therapy adjusted for immunologic risk after heart transplantation.

INTRODUCTION: The efficacy of antithymocyte globulin (ATG) induction in the therapy of immunologically low- and high-risk patients after heart transplantation is not known. METHODS: All patients who received ATG induction from January 2000 through January 2010 were divided into two groups based on the risk of rejection. A higher-risk group (age younger than 60 years, multiparous females, African Americans, panel-reactive antibody >10%, or positive cross-match) received ATG (1.5 mg/kg) for 7 days (ATG7), and the remaining lower-risk group received ATG for 5 days (ATG5), all followed by calcineurin inhibitor, mycophenolate, and prednisone. Endomyocardial biopsies were performed based a standard protocol for up to 3 years after heart transplantation, and for suspected rejection. RESULTS: Of 253 heart transplant recipients, 87 received ATG5 and 166 ATG7. Absolute lymphocyte count <200 per microliter was achieved within 10 days in 88% of ATG5 and 86% of ATG7. Baseline creatinine was 1.3 ± 0.8 pre-transplantation, 1.8 ± 0.9 post-transplantation, and 1.0 ± 0.4 mg/dL at discharge (mean ± standard deviation [SD]; P < .001, compared with pre-transplantation). Of 3667 biopsies, 33 (0.90%) had ≥3A/2R cellular rejection (CR). Of 3599 biopsies, 16 (0.44%) had definite antibody-mediated rejection (AMR). At 5 years, freedom from ≥3A/2R CR (94% ± 2.8% vs 83% ± 7.7%; P = .31) and freedom from AMR (95% ± 2.4% vs 90% ± 6.4%; P = .98) were similar between ATG5 and ATG7, respectively. Survival for ATG5 and ATG7 was comparable at one year (94% ± 2.5% vs 93% ± 2.0%), and at 8 years (61% ± 6.9% and 61% ± 4.7%; P = .88). At 5 years, ATG5 and ATG7 were similar in freedom from cytomegalovirus (CMV) infection (92.3% vs 94.3%; P = not significant [NS]), freedom from pneumonia (83.8% vs 82.1%; P = NS), and in rate of malignancy (excluding skin cancer; 8.0% vs 6.0%; P = NS). CONCLUSIONS: ATG induction therapy (prospectively dose-adjusted for immunologic risk) in low- and high-risk patients results in excellent and equivalent short- and long-term survival rates, with a low incidence of CR and AMR. The use of ATG does not increase rates of CMV infection with appropriate prophylaxis. ATG may benefit renal function by delaying calcineurin inhibitor exposure, and may have a role in the prevention of AMR.

Multiple BM harvests in pediatric donors for thalassemic siblings: safety, efficacy and ethical issues.

Allogeneic BMT represents the only chance of cure for beta-thalassemia. Occasionally, two affected individuals from the same family share a matched healthy sibling. Moreover, a high incidence of transplant rejection is still observed in Pesaro class III patients, requiring a second BMT procedure. In these settings, one option is to perform a second BM harvest from the same donor. Although BM harvest is a safe procedure in children, ethical issues concerning this invasive practice still arise. Here, we describe our series of seven pediatric, healthy donors, who donated BM more than once in favor of their beta-thalassemic HLA-identical siblings between June 2005 and January 2008. Three donors donated BM twice to two affected siblings and four donors donated twice for the same sibling following graft rejection of the first BMT. All donors tolerated the procedures well and no relevant side effects occurred. There was no significant difference between the two harvests concerning cell yield and time to engraftment. Our experience shows that for pediatric donors, a second BM donation is safe and feasible and good cellularity can be obtained. We suggest that a second harvest of a pediatric donor can be performed when a strong indication for BMT exists.

Notes from the field: practical issues in upgrading STD services based on experience from primary healthcare facilities in two Rwandan towns.

OBJECTIVE: In order to assess the feasibility of upgrading STD management at the primary healthcare level in Rwanda, a project was piloted in a health centre and a hospital dispensary in two up country towns. METHODS: Nurses trained in syndrome based management treated all patients with genitourinary complaints at first visit without laboratory results. They provided condom demonstration and risk reduction advice, and gave coupons for partner referral. Principal findings and decisions were recorded on individual patient records. Partners presenting referral coupons were treated presumptively and their records linked to the index case. RESULTS: Three quarters of symptomatic patients seen at the two primary healthcare facilities were women. With training and supervision, nurses applied the syndromic STD management guidelines correctly in over 90% of cases. Symptomatic treatment failure at first follow up visit varied from 0% for male urethritis to 27% for genital ulcer, the one condition that was not treated syndromically. Four fifths of women presenting with vaginal discharge had clinical signs of cervicitis, and the presence of cervical signs was 86% sensitive for presence of leucocytes on cervical Gram stain. CONCLUSIONS: With adequate post-training supervision, nurses were able to apply the syndromic STD management guidelines and a high degree of clinical improvement was achieved. Syndromic algorithms that recommend treatment for all common pathogens at the first visit had higher rates of symptomatic cure at follow up than the algorithm employing a sequential treatment approach. Clinical and laboratory evidence suggests a high prevalence of cervicitis in this population of women seeking care.

Partner referral as a component of integrated sexually transmitted disease services in two Rwandan towns.

OBJECTIVE: To document partner referral rates at health centres with improved STD services, and to determine factors contributing to successful referral. METHODS: Partner referral was initiated as part of the upgrading of STD services in primary care health facilities in two semi-urban Rwanda towns. After syndromic management of the presenting complaint, index patients received prevention education and condom demonstration, and were urged to refer sexual partners to the health centre for a free examination. Partner referral coupons linked by code number to the symptomatic index patient were given to facilitate referral; no identifying information was collected on partners from the index patients. RESULTS: Three quarters of the symptomatic patients seen at the two primary health care facilities were women. Overall, the ratio of referred partners to index patients was 26%. Only 58% of index patients accepted partner referral coupons. The referral rate for those who did accept coupons was 45%. Partner referral worked best for regular partners. Most index patients and partners were married and only four index patients referred more than one partner. Women index patients, especially when pregnant, were more successful in referring partners than men. Index patients who referred partners tended to be older than those who did not. Awareness of STD symptoms in the partner, and diagnosis of cervicitis were associated with a higher rate of STD symptoms in the partner, and diagnosis of cervicitis were associated with a higher rate of partner referral. CONCLUSIONS: Efforts to improve rates of partner referral should begin at the clinic level with improved counselling to convince more index patients of the importance of partner referral. Partner symptom recognition may be useful for increasing rates of partner referral. Supplementary strategies are needed to reach non-regular partners. When syndromic management is used, counselling should take into account the lower predictive values of identifying STD in women in order to avoid partner accusation. Despite limitations, patient referral of sexual partners can be an effective strategy for reaching a population at high risk for STD with minimal additional investment in health worker staff time.

PIP: Partner notification was introduced to primary care health facilities in two semi-urban Rwandan towns as part of an effort to upgrade sexually transmitted disease (STD) services and develop guidelines for STD management. Of the 427 STD patients seen at these two centers in a six-month period in 1993-94, 325 (76%) were women; 31% of these women were pregnant. STD patients were provided with syndromic treatment, STD prevention education, and condom demonstration and were urged to refer their sexual partners to the health center for free STD examination and treatment. Overall, 110 sexual partners (26%) attended the clinics as a result of this intervention. However, only 248 STD patients (58%) accepted partner referral coupons, which included the index patient's identification number and a code for the STD syndrome involved. The referral rate among those who did accept the coupons was 45%. Among the referred partners, 89 (81%) were men and 21 (19%) were women. The rates of both coupon acceptance and partner referral were highest among pregnant women (72% and 33%, respectively). 16 female (76%) and 26 male (29%) partners referred were symptomatic. Awareness of STD symptoms in the partner and a diagnosis of cervicitis were associated with higher referral rates. Partner referral was not very effective in identifying casual contacts--more instrumental to the chain of STD transmission in a community than regular partners. None of the men seen, even those who admitted multiple partners, referred more than one sexual partner for treatment; four women referred casual as well as regular partners. Experience from other studies suggests couples are more accepting of and compliant with partner treatment recommendations when they are framed in the context of treating reproductive tract infections and preserving health and fertility.